Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which is part of a cascade of interacting agents involved in the relaxation of vascular smooth muscle. EDRF is thus important in the control of vascular resistance to blood flow and in the control of blood pressure. Some vasodilators act by causing EDRF to be released from endothelial cells. (See Furchgott, Ann. Rev. Pharmacol. Toxicol. 24, 175-197, 1984.) Recently, Palmer et al. have presented evidence suggesting that EDRF is identical to the simple molecule, nitric oxide, NO (Nature 317, 524-526, 1987), though there remains controversy on this point. It has been hypothesized for years that many nitrovasodilators that mimic the effect of EDRF, like glyceryl trinitrate, amyl nitrite, NaNO.sub.2, and sodium nitroprusside (SNP), do so by virtue of their conversion to a common moiety, namely NO, which is also a vasodilator. (See Kruszyna et al., Tox. & Appl. Pharmacol. 91, 429-438, 1987; Ignarro, FASEB J. 3, 31-36, 1989; Ignarro et al., J. Pharmacol. Exper. Therapeutics 218 (3), 739-749, 1981.)
Some of the compounds suitable for use in the method of the present invention are previously described in scientific literature. However, there is no suggestion in the prior art that any of the disclosed compounds are antihypertensive; indeed there is no suggestion in the prior art that they have any pharmaceutical use. Four compounds are described in Reilly, U.S. Pat. No. 3,153,094, and in Longhi and Drago, Inorg. Chem. 2, 85-88, 1963, and four compounds are disclosed in Artsybasheva and Ioffe, J. Org. Chem. U.S.S.R. (Engl. transl., 23, 1056-1060, 1987). Each of these references is incorporated by reference herein in its entirety. The references teach no biological activity for the compounds disclosed.
Related inventions (to the present invention) are described in U.S. patent application Ser. Nos. 07/316,958, filed Feb. 28, 1989 (now U.S. Pat. No. 4,954,526), 07/409,552, filed Sep. 15, 1989 (now U.S. Pat. No. 5,039,705), 07/423,279, filed Oct. 18, 1989, 07/585,793, filed Sep. 20, 1990, 07/743,892, filed Aug. 12, 1991, 07/764,906, filed Sep. 24, 1991, 07/764,908, filed Sep. 24, 1992, 07/858,885, filed Mar. 27, 1992, 07/867,759, filed Apr. 18, 1992, and 07/935,565, filed Aug. 24, 1992, each of which is incorporated herein by reference.